general mechanism of pyridoxal 5'-phosphate-catalyzed aldolic cleavage, racemisation, and transamination reactions, and catalytic mechanism of the transaldimination reaction involving Tyr55, His228, and Arg235, overview. Tyr55 is contributed by the symmetry-related monomer, with respect to the pyridoxal 5'-phosphate-binding subunit, and functions as the general acid-base catalyst in this proton transfer

general mechanism of pyridoxal 5'-phosphate-catalyzed aldolic cleavage, racemisation, and transamination reactions, and catalytic mechanism of the transaldimination reaction involving Tyr55, His228, and Arg235, overview. Tyr55 is contributed by the symmetry-related monomer, with respect to the pyridoxal 5'-phosphate-binding subunit, and functions as the general acid-base catalyst in this proton transfer

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

SHMT is a ubiquitous enzyme and its sequence and structure were conserved during divergent evolution. SHMT belongs to the fold type-I superfamily of PLP-dependent enzymes, a very complex group of proteins arising from an intricate evolutionary process

a shm1 null mutant requires CO2-enriched air to inhibit photorespiration, while a shm2 null mutant does not show any visible impairment, a double-null mutant cannot survive in CO2-enriched air. Residual SHM activity is undetectably low in purified leaf mesophyll mitochondria of the shm1 mutant. In roots, the knockout of SHM1 does not reduce total SHM activity, whereas the knockout of SHM2 significantly lowers total SHM activity

the enzyme regulates the partitioning of 5,10-methylenetetrahydrofolate between the thymidylate and homocysteine remethylation pathways, mitochondrial SHMT-derived one-carbon units are essential for folate-mediated one-carbon metabolism in the cytoplasm

the reaction catalyzed by this enzyme, the reversible transfer of the Cbeta of serine to tetrahydropteroylglutamate, represents a link between amino acid and folates metabolism and operates as a major source of one-carbon units for several essential biosynthetic processes

the reaction catalyzed by this enzyme, the reversible transfer of the Cbeta of serine to tetrahydropteroylglutamate, represents a link between amino acid and folates metabolism and operates as a major source of one-carbon units for several essential biosynthetic processes

the de novo thymidylate biosynthetic pathway forms a multienzyme complex, containing enzymes serine hydroxymethyltransferase 1 and 2alpha, thymidylate synthase, and dihydrofolate reductase, the complex is associated with the nuclear lamina, overview. The de novo thymidylate biosynthetic pathway in mammalian cells translocates to the nucleus for DNA replication and repair. SHMT1 or SHMT2alpha are required for co-localization of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, indicating that SHMT serves as scaffold protein that is essential for complex formation, SHMT1 scaffold function can determine de novo thymidylate synthesis capacity, SHMT1 interaction with TYMS and DHFR is DNA-dependent, but the formation of thymidylate biosynthesis complex is nucleotide-independent. Folate-mediated one-carbon metabolism in the cytoplasm and nucleus, overview

key role for serine and glycine metabolism in the survival of brain cancer cells within the ischemic zones of gliomas. Glycine decarboxylase inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by glycine decarboxylase can be converted to the toxic molecules aminoacetone and methylglyoxal. SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumor regions

the mitochondrial isoform SHMT2 is a crucial factor in the serine/glycine metabolism in several cancer cell types. Correlation of expression level of SHMT2 and other clinicopathological param­eters in clinical breast cancer, overview

the UV-induced increase in SHMT1 translation is accompanied by an increase in the small ubiquitin-like modifier-dependent nuclear localization of the de novo thymidylate biosynthesis pathway and a decrease in DNA strand breaks, suggesting that SHMT1 plays a role in DNA repair

the reaction catalyzed by this enzyme, the reversible transfer of the Cbeta of serine to tetrahydropteroylglutamate, represents a link between amino acid and folates metabolism and operates as a major source of one-carbon units for several essential biosynthetic processes, e.g. as a primary source of the one carbon units required for the synthesis of thymidylate, purines, and methionine. SHMT also catalyzes the hydrolysis of 5,10-methenyl-tetrahydropteroylglutamate to 5-formyl-tetrahydropteroylglutamate, which serves as a storage form of reduced folates and one-carbon groups in cells in a dormant stage

the reaction catalyzed by this enzyme, the reversible transfer of the Cbeta of serine to tetrahydropteroylglutamate, represents a link between amino acid and folates metabolism and operates as a major source of one-carbon units for several essential biosynthetic processes, e.g. as a primary source of the one carbon units required for the synthesis of thymidylate, purines, and methionine. SHMT also catalyzes the hydrolysis of 5,10-methenyl-tetrahydropteroylglutamate to 5-formyl-tetrahydropteroylglutamate,which serves as a storage formof reduced folates and onecarbon groups in cells in a dormant stage

functional redundancy of SHMT2alpha and SHMT1 in nuclear de novo thymidylate synthesis. The de novo thymidylate biosynthetic pathway forms a multienzyme complex, containing enzymes serine hydroxymethyltransferase 1 and 2alpha, thymidylate synthase, and dihydrofolate reductase, the complex is associated with the nuclear lamina, overview. The de novo thymidylate biosynthetic pathway in mammalian cells translocates to the nucleus for DNA replication and repair. SHMT1 or SHMT2alpha are required for co-localization of dihydrofolate reductase, SHMT, and thymidylate synthase to the nuclear lamina, indicating that SHMT serves as scaffold protein that is essential for complex formation. SHMT expression is rate-limiting for de novo thymidylate synthesis

serine hydroxymethyltransferases are important enzymes of cellular one-carbon metabolism and are essential for the photorespiratory glycine-into-serine conversion in leaf mesophyll mitochondria. SHM1 is the photorespiratory isozyme. Due to exclusion of SHM2 from the photorespiratory environment of mesophyll mitochondria, SHM2 cannot substitute for SHM1 in photorespiratory metabolism. SHM1 and SHM2 operate in a redundant manner in one-carbon metabolism of nonphotorespiring cells with a high demand of one-carbon units, e.g. during lignification of vascular cells, detailed overview

mitochondrial serine hydroxymethyltransferase seems to be fundamental to sustain cancer metabolism since production of glycine fuels heme biosynthesis and therefore oxidative phosphorylation. Respiration of cancer cells may then ultimately rely on endogenous glycine synthesis by mitochondrial serine hydroxymethyltransferase. The link between mitochondrial serine hydroxymethyltransferase activity and heme biosynthesis represents an important aspect of cancer cell metabolism. Glycine itself, rather than one-carbon units deriving from the SHMT2 reaction, is specifically critical in cancer cells

SHMT2 is required for cancer cells to adapt to the tumor environment, but also renders these cells sensitive to glycine cleavage system inhibition. The enzyme has a key role in cells in environments with limited oxygen or nutrient levels

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the 5,10-methylenetetrahydropteroylglutamate-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

SHMTs are an important group of pyridoxal-5'-phosphate-dependent enzymes that catalyze the reversible conversion of L-serine and tetrahydropteroylglutamate to glycine and 5,10-methylenetetrahydropteroylglutamate. The enzyme plays a central role in one-carbon unit metabolism. SHMT also catalyzes the H4PteGlu-independent cleavage of many 3-hydroxyamino acids and the decarboxylation of aminomalonate, at rates similar to that of H4PteGlu-dependent serine cleavage

amino acid residues important for the structure and function of SHMT are Y56, D202, and K231 for the interaction with pyridoxal 5'-phosphate, R64 and D73 for inter-subunit interaction, H127 for cofactor binding, and P258 and R363 for substrate interaction

both PfSHMTc and PfSHMTm show dynamic, stage-dependent localization among the different compartments of the parasite and sequence analysis suggests they may also reversibly associate with each other, a factor that may be critical to folate cofactor function, given the apparent lack of enzymic activity of PfSHMTm

the enzyme psychrophilic shows high catalytic activity at low temperature and thermolability, three-dimensional structure analysis and structure-function relationship, homology modeling of the holoenzyme form, overview. The apoform enzyme is in an open conformation and possesses four or five (in chain A) disordered loops that interact with the cofactor. Cofactor binding triggers a rearrangement of the small domain that moves toward the large domain and screens the pyridoxal 5'-phosphate binding site at the solvent side

the enzyme psychrophilic shows high catalytic activity at low temperature and thermolability, three-dimensional structure analysis and structure-function relationship, homology modeling of the holoenzyme form, overview. The apoform enzyme is in an open conformation and possesses four or five (in chain A) disordered loops that interact with the cofactor. Cofactor binding triggers a rearrangement of the small domain that moves toward the large domain and screens the pyridoxal 5'-phosphate binding site at the solvent side

the enzyme also catalyzes the formation of methylene-tetrahydromethanopterin from tetrahydromethanopterin and L-serine, albeit with a catalytic efficiency which is less than 1% of that with (6S)-tetrahydrofolate as substrate. The catalytic efficiency with methylene-tetrahydrosarcinapterin as substrate is even lower

the enzyme also catalyzes the formation of methylene-tetrahydromethanopterin from tetrahydromethanopterin and L-serine, albeit with a catalytic efficiency which is less than 1% of that with (6S)-tetrahydrofolate as substrate. The catalytic efficiency with methylene-tetrahydrosarcinapterin as substrate is even lower

adding 2fold more glycine in the medium increases significantly the expression of SHMT-S and to an even higher level, the expression of SHMT-L, adding 2fold more serine has the reverse effect on the expression of SHMT-L, while the expression of SHMT-S does not change significantly

SHMT antisense plants display lower photosynthetic capacity and accumulate glycine in light, glycine is converted to serine in the second half of the light period, serine shows an inverse diurnal rhythm and reaches highest values in darkness, glycine/serine conversion is independent of light in the transformant, but not in the wild-type

SHMT1 functions in the photorespiratory pathway and plays a critical role in controlling the cell damage provoked by abiotic stresses such as high light and salt and in restricting pathogen induced cell death

SHMT1 functions in the photorespiratory pathway and plays a critical role in controlling the cell damage provoked by abiotic stresses such as high light and salt and in restricting pathogen induced cell death

SHMT activity with beta-phenylserine as substrate is about 1.48fold and 1.25fold higher than that with beta-(methylsulfonylphenyl) serine and beta-(nitrophenyl) serine as substrate, respectively. Besides SHMT activity, the enzyme also shows L-allo-threonine aldolase activity, EC 4.1.2.48

SHMT activity with beta-phenylserine as substrate is about 1.48fold and 1.25fold higher than that with beta-(methylsulfonylphenyl) serine and beta-(nitrophenyl) serine as substrate, respectively. Besides SHMT activity, the enzyme also shows L-allo-threonine aldolase activity, EC 4.1.2.48

serine hydroxymethyltransferase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes a hydroxymethyl group transfer from L-serine to tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate

SHMT1 functions in the photorespiratory pathway and plays a critical role in controlling the cell damage provoked by abiotic stresses such as high light and salt and in restricting pathogen induced cell death

SHMT1 functions in the photorespiratory pathway and plays a critical role in controlling the cell damage provoked by abiotic stresses such as high light and salt and in restricting pathogen induced cell death

serine hydroxymethyltransferase is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes a hydroxymethyl group transfer from L-serine to tetrahydrofolate to yield glycine and 5,10-methylenetetrahydrofolate